Through the proposed research, we will determine the mechanisms by which Parasympathetic fibers of the vagus nerve exert their rate-controlling influence on the heart. We will investigate the influence of the vagus nerve on membrane potentials and specific ionic channels that operate during pacemaker activity in the sinoatrial node of mammalian heart. New voltage-clamp techniques will be utilized in this study. The role of electrogenic sodium pumping in pacemaker activity and vagal modulation of pacemaker activity will also be investigated. The mathematical model for pacemaker activity in Purkinje fibers will be modified so as to more accurately represent the ionic events that occur during pacemaker activity in the sinoatrial node pacemaker. The effects of electrogenic sodium pumping (ouabain) and of vagal stimulation (acetylcholine) will be quantitatively incorporated into the model.